Abstract: :
Purpose: Lentivirus vector, having a feature of long–termgene expression, is expected as a useful therapeutic methodfor slowly progressive retinal degeneration. We recently developeda novel lentivirus vector derived from the non–pathogenicsimian immunodeficiency virus (SIV), and have demonstrated thatSIV vector can be efficiently and safely applicable to retinalgene transfer and have highly therapeutic effect following PEDFgene expression in RCS rats. We assessed the effect of SIV–mediatedsubretinal gene transfer of basic fibroblast growth factor (FGF2),a potent neurotrophic factor, during the disease progressionin two different animal models, RCS rats and rds mice.Methods: Vector injection into the peripheral subretinal spaceof 3 weeks old RCS rats and rds mice was performed. Histopathologicaland electroretinographic (ERG) assessment were examined at severalperiods up to 24 weeks after gene transfer.Results: In RCS rats, FGF2 gene transfer significantly protectedthe loss of PCs corresponding to the regions of the gene transfercompared to those of control groups until 8 weeks after genetransfer. B–waves of ERGs were significantly observedin the group of SIV–FGF2 treated rats. In rds mice, similarly,histological photoreceptor cell loss and electroretinographicalfunctional defect were significantly prevented at 24 weeks aftergene transfer.Conclusions: SIV–medeated gene transfer of FGF2 can protectthe retinal degeneration and functional defects in two differentanimal models for a long period. These results support the utilityof this neuroprotective gene thrapy against RP, caused by variousgene mutations.